2w3x

Crystal structure of a bifunctional hotdog fold thioesterase in enediyne biosynthesis, CalE7

spinqualitylabelsall models 2w3x, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w3x is a 6 chain structure with sequence from Micromonospora echinospora. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: GOL, JEF, PO4, POP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8KNG2_MICEC Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The biosynthesis of the enediyne moiety of the antitumor natural product calicheamicin involves an iterative polyketide synthase (CalE8) and other ancillary enzymes. In the proposed mechanism for the early stage of 10-membered enediyne biosynthesis, CalE8 produces a carbonyl-conjugated polyene with the assistance of a putative thioesterase (CalE7). We have determined the x-ray crystal structure of CalE7 and found that the subunit adopts a hotdog fold with an elongated and kinked substrate-binding channel embedded between two subunits. The 1.75-A crystal structure revealed that CalE7 does not contain a critical catalytic residue (Glu or Asp) conserved in other hotdog fold thioesterases. Based on biochemical and site-directed mutagenesis studies, we proposed a catalytic mechanism in which the conserved Arg(37) plays a crucial role in the hydrolysis of the thioester bond, and that Tyr(29) and a hydrogen-bonded water network assist the decarboxylation of the beta-ketocarboxylic acid intermediate. Moreover, computational docking suggested that the substrate-binding channel binds a polyene substrate that contains a single cis double bond at the C4/C5 position, raising the possibility that the C4=C5 double bond in the enediyne moiety could be generated by the iterative polyketide synthase. Together, the results revealed a hotdog fold thioesterase distinct from the common type I and type II thioesterases associated with polyketide biosynthesis and provided interesting insight into the enediyne biosynthetic mechanism. Structure and catalytic mechanism of the thioesterase CalE7 in enediyne biosynthesis.,Kotaka M, Kong R, Qureshi I, Ho QS, Sun H, Liew CW, Goh LP, Cheung P, Mu Y, Lescar J, Liang ZX J Biol Chem. 2009 Jun 5;284(23):15739-49. Epub 2009 Apr 8. PMID:19357082 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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